title: A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice.
abstract: OBJECTIVE
  A European randomized trial showed biochemical effects of 6-month treatment with Stronger Neo-Minophagen C (SNMC), a glycyrrhizin-containing preparation, in patients with chronic hepatitis C, but its underlying mechanisms remain elusive. We reported previously that SNMC exhibits an anti-oxidative effect in hepatitis C virus (HCV) transgenic mice that develop marked hepatic steatosis with mitochondrial injury under iron overloading. Hepatic steatosis and iron overload are oxidative stress-associated pathophysiological features in chronic hepatitis C. The aim of this study was to investigate whether long-term treatment with SNMC could prevent the development of hepatic steatosis in iron-overloaded HCV transgenic mice.
  
  
  METHODS
  C57BL/6 transgenic mice expressing the HCV polyprotein were fed an excess iron diet concomitantly with intraperitoneal injection of saline, SNMC, or seven-fold-concentrated SNMC thrice weekly for 6 months.
  
  
  RESULTS
  Stronger Neo-Minophagen C inhibited the development of hepatic steatosis in a dose-dependent manner without affecting hepatic iron content, attenuated ultrastructural alterations of mitochondria of the liver, activated mitochondrial β-oxidation with increased expression of carnitine palmitoyl transferase I and decreased the production of reactive oxygen species in the liver in iron-overloaded transgenic mice. However, SNMC hardly affected the unfolded protein response, which post-transcriptionally activates sterol regulatory element-binding protein 1, a transcription factor involved in lipid synthesis, even though we reported previously the activation of the unfolded protein response in the same iron-overloaded transgenic mice.
  
  
  CONCLUSIONS
  These results suggest that SNMC prevents hepatic steatosis possibly by protecting mitochondria against oxidative stress induced by HCV proteins and iron overload.
authors.affiliation: Department of Hepatology and Pancreatology, Kawasaki Medical University, Okayama, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Korenaga
authors.forename: Isao
authors.initials: I
authors.lastname: Hidaka
authors.forename: Sohji
authors.initials: S
authors.lastname: Nishina
authors.forename: Aya
authors.initials: A
authors.lastname: Sakai
authors.forename: Akane
authors.initials: A
authors.lastname: Shinozaki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Gondo
authors.forename: Takakazu
authors.initials: T
authors.lastname: Furutani
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kawano
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hino
mesh_terms: D000818:Animals; D003545:Cysteine / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D005998:Glycine / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006526:Hepatitis C / Q000150:complications*; D015151:Immunoblotting; D007501:Iron / Q000378:metabolism; D019266:Iron, Dietary; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D004338:Drug Combinations; D019266:Iron, Dietary; D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1; D019695:Glycyrrhizic Acid; C083319:stronger neominophagen C; D007501:Iron; D003545:Cysteine; D006034:Glycyrrhetinic Acid; D005998:Glycine